P671: TREATMENT SEQUENCES AND OUTCOMES OF PATIENTS WITH CLL TREATED WITH TARGETED AGENTS IN REAL-WORLD SETTINGS
Authors: A. R. Mato, B. S. Manzoor, C. C. Coombs, N. Lamanna, H. H. Tuncer, J. R. Brown, L. E. Roeker, M. Shadman, J. N. Allan, C. Ujjani, B. Eichhorst, L. Leslie, I. Fleury, H. Alhasani, J. Rhodes, B. T. Hill, P. M. Barr, A. Skarbnik, M. S. Davids, R. Bannerji, M. Fuldeore, F. Lansigan, A. Schuh, L. Pearson, C. P. Fox, I. Pivneva, L. Popadic, A. Guerin, T. A. Eyre
Journal: HemaSphere (2022)

Background: Treatment (tx) options for patients (pts) with chronic/small lymphocytic leukemia (CLL/SLL) have expanded following regulatory approval of targeted agents. However, real-world evidence regarding pt outcomes and tx sequences is evolving. Aims: We assessed tx trends, sequences and outcomes following the introduction of targeted agents. Methods: The CLL Collaborative Study of Real-World Evidence (CORE), a retrospective, international, observational study (23 centers) for CLL/SLL pts provided data for this analysis. Pts were diagnosed with CLL/SLL, treated in the relapsed/refractory (R/R) setting after 2/12/2014. Tx sequences following targeted agents (ie, BTKi: acalabrutinib, ibrutinib; BCL2i: venetoclax), clinical response (physician-assessed in medical charts and reported as overall response rate [ORR]), and progression-free survival (PFS) were assessed. Results: Of the 1,624 study pts, in 1L 48.8% initiated CT/CIT, 40.6% targeted agents (BTKi: 32.6%; BCL2i: 4.5%), and 10.6% other therapies. We observed 1L CT/CIT use decreased starting 2014 (pre-2014: 58.1%; 2014–2016: 46.0%; 2017–2019: 24.6%; 2020–2021: 0%), while 1L targeted agent use increased over time (pre-2014: 30.5%; 2014–2016: 43.1%; 2017–2019: 67.0%; 2020–2021: 94.7%). Post-targeted agent introduction in 2014, the most frequent tx sequence has changed from 1L CT/CIT→BCRi in 2014–2016 to 1L BCRi→BCL2i in 2017–2021 (Figure 1). Across lines and years of tx, among 650 R/R CLL/SLL pts who initiated therapy >2/12/2014, 536 pts (82.5%) received BTKi-based regimens and 214 pts (32.9%) received BCL2i-based regimens. Of the 536 pts receiving BTKi-based regimens (ibrutinib alone: 454 [85.5%]; acalabrutinib alone: 21 [4.0%]), majority was in 2L and 3L+ (291 pts (54.3%); 167 pts (31.2%), respectively). Of the 457 pts with response assessed, 343 pts (75.1%) achieved ORR in the line of therapy (LOT) with BTKi-based regimen. The median PFS for pts receiving BTKi-based regimen was 36.4 months (95% confidence interval [CI]: 33.1, 41.9). 236 pts (44.0%) receiving a BTKi-based regimen had a subsequent LOT; of the 177 pts with response assessed, 120 pts (67.8%) achieved ORR. The most common subsequent tx were BCL2i-based (N=113; ORR: 76.2%) or another BTKi-based (N=41; ORR: 54.8%) regimens. Of the 214 pts receiving BCL2i (venetoclax alone: 129 [60.3%]), majority was in 2L and 3L+ (77 pts [36.0%] and 132 pts [61.7%], respectively). Of the 164 pts with response assessed, 127 pts (77.4%) achieved ORR in the LOT with BCL2i-based regimen. The median PFS for pts receiving BCL2i was 26.2 months (95% CI: 20.0, 38.7). 47 pts (22.0%) receiving BCL2i had a subsequent LOT; of the 37 pts with response assessed, 27 pts (73.0%) achieved ORR. The most common subsequent tx were BTKi-based (ibrutinib-based regimen: 14 [29.8%]; acalabrutinib-based regimen: 5 [10.6%]; ORR: 76.9%) or another BCL2i-based (venetoclax-based re-tx: 8 [17.8%]; ORR: 80.0%) regimens. Image:Summary/Conclusion: 1L CT/CIT use is declining since 2014 and 1L targeted agent use is now the standard of care in real-world practice. Of currently available targeted therapies, ibrutinib was the most commonly used. These results demonstrate sequences of BTKi use following venetoclax (venetoclax→BTKi) are effective, as well rechallenging with venetoclax (venetoclax→venetoclax), providing support for either strategy in the R/R CLL/SLL management. These results provide clinicians with valuable insights regarding pt outcomes associated with different tx sequences currently considered in modern clinical practice. Updated pt level data and survival analyses are underway.